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The Serine/Theorine Phosphatase PP4 Is Requiered for Pro-B Cell Development through Its Promotion of Immunoglobulin VDJ Recombination

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Su,  Yu-wen
Research Group and Chair of Molecular Immunology of the University of Freiburg, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Chen,  Ming-yu
Max Planck Society;

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Citation

Su, Y.-w., Chen, Y.-p., Chen, M.-y., & Tan, T.-H. (2013). The Serine/Theorine Phosphatase PP4 Is Requiered for Pro-B Cell Development through Its Promotion of Immunoglobulin VDJ Recombination. PLoS ONE, 8, e68804-e68804.


Cite as: http://hdl.handle.net/11858/00-001M-0000-002B-893B-9
Abstract
PP4 phosphatase regulates a number of crucial processes but the role of PP4 in B cells has never been reported. We generated B cell-specific pp4 knockout mice and have identified an essential role for PP4 in B cell development. Deficiency of PP4 in B lineage cells leads to a strong reduction in pre-B cell numbers, an absence in immature B cells, and a complete loss of mature B cells. In PP4-deficient pro-B cells, immunoglobulin (Ig) DJH recombination is impaired and Ig µ heavy chain expression is greatly decreased. In addition, PP4-deficient pro-B cells show an increase of DNA double-strand breaks at Ig loci. Consistent with their reduced numbers, residual PP4-deficient pre-B cells accumulate in the G1 phase, exhibit excessive DNA damage, and undergo increased apoptosis. Overexpression of transgenic Ig in PP4-deficient mice rescues the defect in B cell development such that the animals have normal numbers of IgM+ B cells. Our study therefore reveals a novel function for PP4 in pro-B cell development through its promotion of VHDJH recombination.